Effect of fucoxanthin on the MAPKs signaling pathway and induction of apoptosis in B16F10 melanoma cells

Abstract

Fucoxanthin, a natural carotenoid, has been reported to have antitumorigenic activity in mouse colon, skin and duodenum models. The present study was designed to evaluate the molecular mechanisms of fucoxanthin against melanoma cell lines (B16F10 cells). Fucoxanthin reduced the viability of B16F10 cells in a dose-dependent manner accompanied by the induction of cell cycle arrest during the G0/G1 phase and apoptosis. Fucoxanthin-induced G0/G1 arrest was associated with a marked decrease in the protein expressions of phosphorylated-Rb (retinoblastoma protein), cyclin D(1 and 2) and cyclin-dependent kinase (Cdk)4 and up-regulation of the protein levels of p15INK4B and p27Kip1. Fucoxanthin-induced apoptosis was accompanied with down-regulation of the protein levels of Bcl-xL, and inhibitor of apoptosis protein (XIAP), resulting in cytochrome c release and sequential activation of caspase-9, caspase-3, and PARP. Furthermore, fucoxanthin activated c-Jun N-terminal kinase (JNK), p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) on B16F10 cells in a time-dependent manner. These results suggest that fucoxanthin has anti-tumor properties on melanoma cells by inducing selectively the genes related to cell cycle arrest and apoptosis.